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Toward the Development of a General Chiral Auxiliary. A Total Synthesis of (+)-Tetronolide via a Tandem Ketene-Trapping [4 + 2] Cycloaddition Strategy

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Contribution from the Department of Chemistry, University of Rochester, P.O. Box 270216, Hutchison Hall, Rochester, New York 14627-0216
Cite this: J. Am. Chem. Soc. 2006, 128, 32, 10572–10588
Publication Date (Web):July 21, 2006
Copyright © 2006 American Chemical Society

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    A highly convergent, enantioselective total synthesis of the aglycone of the tetrocarcins, (+)-tetronolide, is described. The synthesis highlights the use of several new methods, including camphor auxiliary-directed asymmetric alkylation and the enantioselective preparation of acyclic mixed acetals bearing chirality at the acetal center, and the highly efficient connection of the two major precursors via a ketene-trapping/intramolecular [4 + 2] cycloaddition strategy.


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    Experimental procedures for numbered intermediates 9, 12, 13, 1619, 2931, 33, 34, 3639, and 41 along with unnumbered isolated intermediates. Copies of 1H NMR and most IR spectra for numbered intermediates 57, 9,1214, 1619, 21, 2326, 2834, 3639, 41, 43, 45, 47, 50, 51, 53, and 54 and unnumbered isolated intermediates; 1H NMR spectra of our synthetic, Yoshii's synthetic, and natural tetronolide (+)-1, and X-ray crystallographic data for diol 46. This material is available free of charge via the Internet at

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